A Phase I Randomized, Controlled, Clinical Trial of Valganciclovir in Idiopathic Pulmonary Fibrosis

Human herpesviruses Epstein-Barr virus and cytomegalovirus are frequently detectable in the lungs of patients with idiopathic pulmonary fibrosis (IPF) and could contribute to disease pathogenesis. With the goal of inhibiting herpesvirus replication, we tested the safety and tolerability of adding valganciclovir to standard IPF therapy (pirfenidone). We performed a single-center, Phase I, double-blind, randomized, placebo-controlled trial comparing valganciclovir 900 mg daily with placebo in patients with IPF with serologic evidence of prior Epstein-Barr virus and/or cytomegalovirus infection who were tolerating full-dose pirfenidone (2,403 mg/d). Subjects were randomized to valganciclovir or placebo 2:1 for 12 weeks of active treatment with off-treatment follow-up for up to 12 months. The primary safety endpoint was the number of subjects discontinuing the study drug before completing 12 weeks of treatment. Thirty-one subjects with IPF were randomized to valganciclovir ( = 20) or placebo ( = 11). All subjects completed assigned therapy except one subject in the valganciclovir group, who discontinued the study drug after developing a rash. The total number of adverse events was similar between study groups. In a prespecified analysis of secondary physiologic endpoints, we observed a trend toward improved forced vital capacity from randomization to Week 12 in valganciclovir-treated subjects (-10 ml; interquartile range [IQR], -65 to 70 ml) versus placebo-treated subjects (40 ml; IQR, -130 to 60 ml), which persisted through 12 months of follow-up. Valganciclovir is safe and well tolerated as an add-on therapy to pirfenidone in patients with IPF. Clinical trial registered with ClinicalTrials.gov (NCT02871401).